title: Plant-made trastuzumab (herceptin) inhibits HER2/Neu+ cell proliferation and retards tumor growth.
abstract: BACKGROUND
  Plant biotechnology provides a valuable contribution to global health, in part because it can decrease the cost of pharmaceutical products. Breast cancer can now be successfully treated by a humanized monoclonal antibody (mAb), trastuzumab (Herceptin). A course of treatment, however, is expensive and requires repeated administrations of the mAb. Here we used an Agrobacterium-mediated transient expression system to produce trastuzumab in plant cells.
  
  
  RESULTS
  We describe the cloning and expression of gene constructs in Nicotiana benthamiana plants using intron-optimized Tobacco mosaic virus- and Potato virus X-based vectors encoding, respectively, the heavy and light chains of trastuzumab. Full-size antibodies extracted and purified from plant tissues were tested for functionality and specificity by (i) binding to HER2/neu on the surface of a human mammary gland adenocarcinoma cell line, SK-BR-3, in fluorescence-activated cell sorting assay and (ii) testing the in vitro and in vivo inhibition of HER-2-expressing cancer cell proliferation. We show that plant-made trastuzumab (PMT) bound to the Her2/neu oncoprotein of SK-BR-3 cells and efficiently inhibited SK-BR-3 cell proliferation. Furthermore, mouse intraperitoneal PMT administration retarded the growth of xenografted tumors derived from human ovarian cancer SKOV3 Her2+ cells.
  
  
  CONCLUSIONS
  We conclude that PMT is active in suppression of cell proliferation and tumor growth.
authors.affiliation: A.N. Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Komarova
authors.forename: Vyacheslav S
authors.initials: VS
authors.lastname: Kosorukov
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Frolova
authors.forename: Igor V
authors.initials: IV
authors.lastname: Petrunia
authors.forename: Ksenia A
authors.initials: KA
authors.lastname: Skrypnik
authors.forename: Yuri Y
authors.initials: YY
authors.lastname: Gleba
authors.forename: Yuri L
authors.initials: YL
authors.lastname: Dorokhov
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000473:pathology; D010455:Peptides / Q000276:immunology; D018515:Plant Leaves / Q000187:drug effects / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D014026:Nicotiana / Q000378:metabolism*; D000068878:Trastuzumab; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000939:Epitopes; D010455:Peptides; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab